1-6628560-T-C

Variant names:

• chr1-6628560-T-C
• NM_001195753.2:c.136T>C
• THAP3 p.Phe46Leu

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001195753.2(THAP3):​c.136T>C​(p.Phe46Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: THAP3 NM_001195753.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86
• Publications: 0 publications found

Genes affected

THAP3 (HGNC:20855): (THAP domain containing 3) Predicted to enable DNA binding activity and metal ion binding activity. Involved in positive regulation of transcription by RNA polymerase II. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.901

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195753.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP3	NM_001195753.2	MANE Select	c.136T>C	p.Phe46Leu	missense	Exon 3 of 6	NP_001182682.1	Q8WTV1-1
	THAP3	NM_001394496.1		c.136T>C	p.Phe46Leu	missense	Exon 2 of 5	NP_001381425.1
	THAP3	NM_001195752.2		c.136T>C	p.Phe46Leu	missense	Exon 3 of 6	NP_001182681.1	Q8WTV1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP3	ENST00000054650.9	TSL:1 MANE Select	c.136T>C	p.Phe46Leu	missense	Exon 3 of 6	ENSP00000054650.4	Q8WTV1-1
	THAP3	ENST00000922199.1		c.136T>C	p.Phe46Leu	missense	Exon 2 of 5	ENSP00000592258.1
	THAP3	ENST00000866305.1		c.136T>C	p.Phe46Leu	missense	Exon 2 of 5	ENSP00000536364.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.59	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Benign	1.5	L
PhyloP100		5.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.024	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.63
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-6688620;